TY  - JOUR
AU  - Miletić, Tijana
AU  - Kyriakos, Kachrimanis
AU  - Graovac, Adrijana
AU  - Ibrić, Svetlana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1841
AB  - The present work investigates the effect of complexation with hydroxypropyl-beta-cyclodextrin (HPBCD) and 2-O-methyl-beta-cyclodextrin (2-O-MBCD), on voriconazole solubility, dissolution rate and chemical stability. Drug-cyclodextrin complexes were prepared as aqueous solutions, which were spray-dried, and their properties were compared to wet ground samples and physical mixtures. DSC analysis revealed absence of crystalline voriconazole from spray-dried complexes. FTIR spectroscopy indicated changes in the H-bonding network of the hydroxyl groups of cyclodextrin following drug inclusion. Dissolution rate of voriconazole was significantly higher from spray-dried complexes with either cyclodextrin in comparison with free drug, physical mixtures, or wet ground mixtures. However, two degradation impurities were found in aged samples, with slightly higher impurity level with HPBCD. Performed solubility studies suggested that 2-O-MBCD is more efficient solubilizer. Molecular docking simulations showed a difference in the 1:1 binding affinities and sites, with HPBCD surprisingly forming complexes of much lower energy, thus suggesting a multiple rather than a 1:1 complexation.
PB  - Elsevier Sci Ltd, Oxford
T2  - Carbohydrate Polymers
T1  - Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability
VL  - 98
IS  - 1
SP  - 122
EP  - 131
DO  - 10.1016/j.carbpol.2013.05.084
ER  - 

@article{
author = "Miletić, Tijana and Kyriakos, Kachrimanis and Graovac, Adrijana and Ibrić, Svetlana",
year = "2013",
abstract = "The present work investigates the effect of complexation with hydroxypropyl-beta-cyclodextrin (HPBCD) and 2-O-methyl-beta-cyclodextrin (2-O-MBCD), on voriconazole solubility, dissolution rate and chemical stability. Drug-cyclodextrin complexes were prepared as aqueous solutions, which were spray-dried, and their properties were compared to wet ground samples and physical mixtures. DSC analysis revealed absence of crystalline voriconazole from spray-dried complexes. FTIR spectroscopy indicated changes in the H-bonding network of the hydroxyl groups of cyclodextrin following drug inclusion. Dissolution rate of voriconazole was significantly higher from spray-dried complexes with either cyclodextrin in comparison with free drug, physical mixtures, or wet ground mixtures. However, two degradation impurities were found in aged samples, with slightly higher impurity level with HPBCD. Performed solubility studies suggested that 2-O-MBCD is more efficient solubilizer. Molecular docking simulations showed a difference in the 1:1 binding affinities and sites, with HPBCD surprisingly forming complexes of much lower energy, thus suggesting a multiple rather than a 1:1 complexation.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Carbohydrate Polymers",
title = "Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability",
volume = "98",
number = "1",
pages = "122-131",
doi = "10.1016/j.carbpol.2013.05.084"
}

Miletić, T., Kyriakos, K., Graovac, A.,& Ibrić, S.. (2013). Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability. in Carbohydrate Polymers
Elsevier Sci Ltd, Oxford., 98(1), 122-131.
https://doi.org/10.1016/j.carbpol.2013.05.084

Miletić T, Kyriakos K, Graovac A, Ibrić S. Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability. in Carbohydrate Polymers. 2013;98(1):122-131.
doi:10.1016/j.carbpol.2013.05.084 .

Miletić, Tijana, Kyriakos, Kachrimanis, Graovac, Adrijana, Ibrić, Svetlana, "Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability" in Carbohydrate Polymers, 98, no. 1 (2013):122-131,
https://doi.org/10.1016/j.carbpol.2013.05.084 . .

TY  - JOUR
AU  - Mihajlović, Tijana
AU  - Kachrimanis, Kyriakos
AU  - Graovac, Adrijana
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1753
AB  - Due to the fact that the number of new poorly soluble active pharmaceutical ingredients is increasing, it is important to investigate the possibilities of improvement of their solubility in order to obtain a final pharmaceutical formulation with enhanced bioavailability. One of the strategies to increase drug solubility is the inclusion of the APIs in cyclodextrins. The aim of this study was to investigate the possibility of aripiprazole solubility improvement by inclusion in (2-hydroxy)propyl-beta-cyclodextrin (HPBCD) and simultaneous manipulation of pH of the medium and addition of polyvinylpyrrolidone. Aripiprazole-HPBCD complexes were prepared by spray drying aqueous drug-HPBCD solutions, and their properties were compared with those prepared by solvent-drop co-grinding and physical mixing. The obtained powders were characterized by thermoanalytical methods (TGA and DSC), FTIR spectroscopy, their dissolution properties were assessed, while the binding of aripiprazole into the cavity of HPBCD was studied by molecular docking simulations. The solubilization capacity was found to be dependent on pH as well as the buffer solution's ionic composition. The presence of PVP in the formulation could affect the solubilization capacity significantly, but further experimentation is required before its effect is fully understood. On the basis of solubility studies, the drug/HPBCD stoichiometry was found to be 1:3. The spray-dried products were free of crystalline aripiprazole, they possessed higher solubility and dissolution rate, and were stable enough over a prolonged period of storage. Spray drying of cyclodextrin solutions proved to be an appropriate and efficient technique for the preparation of highly soluble inclusion compounds of aripiprazole and HPBCD.
PB  - Springer, New York
T2  - AAPS PharmSciTech
T1  - Improvement of Aripiprazole Solubility by Complexation with (2-Hydroxy)propyl-beta-cyclodextrin Using Spray Drying Technique
VL  - 13
IS  - 2
SP  - 623
EP  - 631
DO  - 10.1208/s12249-012-9786-3
ER  - 

@article{
author = "Mihajlović, Tijana and Kachrimanis, Kyriakos and Graovac, Adrijana and Đurić, Zorica and Ibrić, Svetlana",
year = "2012",
abstract = "Due to the fact that the number of new poorly soluble active pharmaceutical ingredients is increasing, it is important to investigate the possibilities of improvement of their solubility in order to obtain a final pharmaceutical formulation with enhanced bioavailability. One of the strategies to increase drug solubility is the inclusion of the APIs in cyclodextrins. The aim of this study was to investigate the possibility of aripiprazole solubility improvement by inclusion in (2-hydroxy)propyl-beta-cyclodextrin (HPBCD) and simultaneous manipulation of pH of the medium and addition of polyvinylpyrrolidone. Aripiprazole-HPBCD complexes were prepared by spray drying aqueous drug-HPBCD solutions, and their properties were compared with those prepared by solvent-drop co-grinding and physical mixing. The obtained powders were characterized by thermoanalytical methods (TGA and DSC), FTIR spectroscopy, their dissolution properties were assessed, while the binding of aripiprazole into the cavity of HPBCD was studied by molecular docking simulations. The solubilization capacity was found to be dependent on pH as well as the buffer solution's ionic composition. The presence of PVP in the formulation could affect the solubilization capacity significantly, but further experimentation is required before its effect is fully understood. On the basis of solubility studies, the drug/HPBCD stoichiometry was found to be 1:3. The spray-dried products were free of crystalline aripiprazole, they possessed higher solubility and dissolution rate, and were stable enough over a prolonged period of storage. Spray drying of cyclodextrin solutions proved to be an appropriate and efficient technique for the preparation of highly soluble inclusion compounds of aripiprazole and HPBCD.",
publisher = "Springer, New York",
journal = "AAPS PharmSciTech",
title = "Improvement of Aripiprazole Solubility by Complexation with (2-Hydroxy)propyl-beta-cyclodextrin Using Spray Drying Technique",
volume = "13",
number = "2",
pages = "623-631",
doi = "10.1208/s12249-012-9786-3"
}

Mihajlović, T., Kachrimanis, K., Graovac, A., Đurić, Z.,& Ibrić, S.. (2012). Improvement of Aripiprazole Solubility by Complexation with (2-Hydroxy)propyl-beta-cyclodextrin Using Spray Drying Technique. in AAPS PharmSciTech
Springer, New York., 13(2), 623-631.
https://doi.org/10.1208/s12249-012-9786-3

Mihajlović T, Kachrimanis K, Graovac A, Đurić Z, Ibrić S. Improvement of Aripiprazole Solubility by Complexation with (2-Hydroxy)propyl-beta-cyclodextrin Using Spray Drying Technique. in AAPS PharmSciTech. 2012;13(2):623-631.
doi:10.1208/s12249-012-9786-3 .

Mihajlović, Tijana, Kachrimanis, Kyriakos, Graovac, Adrijana, Đurić, Zorica, Ibrić, Svetlana, "Improvement of Aripiprazole Solubility by Complexation with (2-Hydroxy)propyl-beta-cyclodextrin Using Spray Drying Technique" in AAPS PharmSciTech, 13, no. 2 (2012):623-631,
https://doi.org/10.1208/s12249-012-9786-3 . .